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Progress
In June 2000, scientists announced a stunning achievement: the generation
of a working draft sequence of the entire human genome. The document
was competed 18 months ahead of schedule. This draft provides a
road map to an estimated 909% of genes on every chromosome. It has
already enabled gene hunters to pinpoint genes associated with more
than 30 genetic disorders.
HGP
Goals
From the outset, the ultimate goal of HGP has been to generate a
high-quality reference sequence for the entire human genome and
identify all human genes. There are a number of other HGP goals
HGP goals are to
- identify all the approximate 30,000 genes
in human DNA,
- determine the sequences of the 3 billion
chemical base pairs that make up humanDNA,
- store this information in databases, *
improve tools for data analysis,
- transfer related technologies to the private
sector, and Ý address the ethical, legal, and social issues (ELSI)
that may arise from the project.
- explore gene function through mouse-human
comparisons.
To help achieve these goals, researchers also
are studying the genetic makeup of several nonhuman organisms. These
include the common human gut bacterium Escherichia coli, the fruit
fly, and the laboratory mouse.
Ethical, Legal,
and Social, Implications
A unique aspect of the U.S. Human
Genome Project is that it is the first large scientific undertaking
to address the ethical, legal, and social, implications (ELSI) that
may arise from HGP and the vast increase in the amount of genetic
information.
The
Private and Public Sector
Another important feature of the project is the federal government's
long-standing dedication to the transfer of technology to both the
private and public sector. HGP resources have spurred a boom in
spin-off sequencing programs on the human and other genomes. To
stimulate further research, all data generat4d in the public sector
are made available rapidly and free of charge via the World Wide
Web.
Insights
The draft of the human genome sequence will not be refined to high
quality until 2003, However, there are many insights that gained
so far from HGP research. These insights include:
The Human Genome
- The human genome contains 3164.7 million
chemical nucleotide bases (A, C, T, and G).
- The average gene consists of 3000 bases,
but sizes vary greatly, with the largest known human gene being
dystrophin with 2.4 million bases.
- The total number of genes is estimated
at approximately 30,000, much lower than previous estimates of
80,000 to 140,000 that had been based on extrapolations from gene-rich
areas as opposed to a composite of gene-rich and gene-poor areas.
- The order of almost all (99.9%) nucleotide
bases is exactly the same in all people.
The functions are unknown for more than 50% of discovered genes.
- About 2% of the genome encodes instructions
for the synthesis of proteins.
Repeated sequences that do not code ofr proteins (junk DNA) make
up at least 50% of the human genome.
- Repetitive sequences are thought to have
no direct functions, but they shed light on chromosome structure
and dynamics. Over time, these repeats reshape the genome by rearranging
it, thereby creating entirely new genes or modifying and reshuffling
existing genes.
- During the past 50 million years, a dramatic
decrease seems to have occurred in the rate of accumulation of
these repeats.
- The human genome’s gene-dense “urban
centers” area composed predominantly of the DNA building
blocks G and C.
- In contrast, the gene-poor “deserts”
are rich in the DNA building blocks A and T.
Genes appear to be concentrated in random areas along the genome,
with vast expanses of noncoding DNA between.
- Stretches of up to 30,000 C and G bases
repeating over and over often occur adjacent to gene0rich areas,
forming a barrier between the genes and the “junk DNA.”
These C and G islands are believed to help regulate gene activity.
- Scientists have identified about 1.4 million
locations where singe-based DNA differences (SNPs) occur in humans.
This information promises to revolutionize the processes of finding
chromosomal locations for disease-associated sequences and tracing
human history.
- The ratio of germline (sperm or egg cell)
mutations is 2:1 in males vs females. Researchers point to several
reasons for the higher mutation rate in the male germline, including
the greater number of cell divisions required for sperm formation
than for eggs.
How the Human Genome Compares with Those
of Other Organisms
- Unlike the human’s seemingly random
distribution of gene-rich areas, many other organisms’ genomes
are more uniform, with genes evenly spaced throughout.
- Humans have on average three times as many
kinds of proteins as the fly or worm because of mRNA transcript
“alternative splicing” and chemical modifications tot
he proteins. This process can yield different protein products
from the same gene.
- Humans share most of the same protein families
with worms, flies, and plants, but the number of gene gamily members
has expanded in humans, especially in proteins involved in development
and immunity.
- The human genome has a much greater portion
(50%) of repeat sequences than the mustard week (11%), the worm
(7%), and the fly (3%).
- Although humans appear to have stopped
accumulating repetitive DNA over 50 million years ago, there seems
to be no such decline in rodents. This may account for some of
the fundamental differences between hominids and rodents, although
estimates of gene numbers are similar in both species. Scientists
have proposed many theories to explain evolutionary contrasts
between humans and other organisms, including life span, litter
sizes, inbreeding, and genetic drift.
HGP
and Future Research
HGP is creating an entirely new approach to biological research.
In the past, researchers studied one or a few genes at a time. With
whole-genome sequences and new automated, high-throughput technologies,
they can approach questions systematically and on a grand scale.
Researchers can study all the genes in a genome or all the gene
products in a particular tissue or organ or tumor. They can also
study how tens of thousands of genes and proteins work together
in interconnected networks to orchestrate the chemistry of life.
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